Determination of temperature-dependent optimal oral doses of florfenicol and corresponding withdrawal times in Nile tilapia (Oreochromis niloticus) reared at 25 and 30°C

Abstract

Antimicrobials are important tools for controlling bacterial outbreaks in aquaculture, but their misuse can bring more harms than benefits. For prudent use of antimicrobials, an optimal dosing regimen that is adjustable by rearing temperature and antimicrobial sensitivity are preferred over a universal dosage. The main objective of the present study was to investigate the advantage of using temperature-dependent optimal dosages of florfenicol (FF) on withdrawal time (WDT) reduction compared to a conventional recommended dosage in Nile tilapia. First, the pharmacokinetic (PK) parameters of FF at 25 and 30 °C were determined after a single oral administration of 10 mg/kg FF. Then, the optimal dosing regimens, calculated by the pharmacokinetic-pharmacodynamic (PK-PD) approach with a target minimum inhibitory concentration (MIC) of 3 μg/mL were used to evaluate tissue depletion and WDT. The optimal doses as determined by PK study were 4.46 and 12.60 mg/kg/day for 25 and 30 °C, respectively. Subsequently, the fish were orally administered with FF at the round-up optimal dosages (5 mg/kg/day at 25 °C and 13 mg/kg/day at 30 °C) or a general dosage (10 mg/kg/day at 25 °C) once daily for 5 days for tissue depletion and WDT study. The serum concentrations at 24 h after the last optimal dose were 3.26 (for the 5 mg/kg/day 25 °C) and 3.72 μg/mL (for the 13 mg/kg/day 30 °C), respectively, which were comparable to the target MIC of 3 μg/mL; whereas, the corresponding concentration of the general dosage at 25 °C was 8.06 μg/mL. Using the sum of FF and its major metabolite florfenicol amine (FFA) as the marker residue in the muscle/skin and the maximum residue limit (MRL) of 1 μg/g, the WDT for general dosage was 10 days, whereas those of the optimal dosages were 7–8 days. The current study revealed that overdosing may occur at lower while under-dosing could happen at higher rearing temperature if single general dosage was employed. With the established optimal dosing regimen, serum concentrations could be maintained above the target MIC and the WDT be shortened, a single WDT might be possible using the optimal dosages strategy regardless of water temperature.